DESCRIPTION: (Principal Investigator's) This proposal details the development of new, catalytic reaction methodology for the efficient asymmetric synthesis of polyacetate-derived macrolide antibiotics of potential pharmaceutical interest such as recently discovered powerfully anti-fungal marine natural product leucascandrolide A. It has been documented that drug-resistant bacterial and fungal infections represent a problem of rapidly growing importance. More than simply achieving synthesis of such compounds, the focus of the proposal is on advancing the frontiers of efficiency, waste-minimizing and economic viability of such synthetic efforts. The ultimate goal is thus the realization of practicable and practical chemistry that will affect both the discovery and process phases of research into new medicinal agents. These reactions under consideration have as their unifying theme the stereo-and regioselective transition metal-catalyzed carbonylation of alkenes leading to the direct synthesis of suitably protected/masked 3,5- dihydroxyaldehydes. This represents a novel approach to (1,3,5...) polyol synthesis that will enjoy the benefits that render carbonylation a feasible industrial-scale process.